Melphalan is transported into the L1210 leukemia cell by two high affinity leucine-preferring systems, one sodium ion-independent and a newly characterized sodium-dependent system. Both transport systems are energy dependent and each concentrates melphalan approximately 5-fold. A bicyclic leucine analog, bicyclo(2,2,1)heptane-2-2carboxylic acid or BCH, inhibits leucine uptake only at the sodium ion-independent carrier and is only 50% effective in blocking melphalan uptake and cytotoxicity in L1210 cells. Bone marrow progenitor cells (CFU-C) contain only the leucine-preferring, sodium-dependent, transport system. At cytotoxic concentrations the uptake of melphalan, the D-isomer of melphalan, is determined in part by the leucine-preferring transport system and in part by passive diffusion.